title: Rationale and design of a randomized trial on the impact of aldosterone antagonism on cardiac structure and function in diabetic cardiomyopathy.
abstract: Development of a cardiomyopathy in diabetes mellitus is independent of traditional risk factors, with no clinical trials targeting specific therapeutic interventions. Myocardial fibrosis is one of the key mechanisms and aldosterone is a key mediator of myocardial fibrosis. We propose that aldosterone antagonism will improve cardiac function. We aim to evaluate the efficacy of selective aldosterone receptor antagonism with eplerenone added to optimal medical treatment in improving cardiac structure and function in diabetic cardiomyopathy. We will randomize 130 patients with type 2 diabetes mellitus, stable metabolic control and impaired left ventricular (LV) systolic or diastolic function, to either eplerenone (target dose 50mg) or matching placebo, in addition to optimal medical therapy for 12 months. The primary endpoints are changes in LV systolic and diastolic function, measured by echocardiographic 2-dimensional speckle tracking strain and strain rate and tissue Doppler imaging. The secondary endpoints include changes in echocardiographic markers and plasma biomarkers of collagen turnover; left atrial dimensions and function, incidence of atrial fibrillation and changes in exercise capacity and dyspnea score. The present study will assess whether specific aldosterone antagonism with eplerenone in addition to standard therapy will prevent progression or reverse cardiac dysfunction in diabetic cardiomyopathy using sensitive, robust and quantifiable echocardiographic measures that allow early detection of change. The study may offer a new direction in the management of this condition.
  
  
  BACKGROUND
  ACTRN12610001063000.
authors.affiliation: Department of Cardiology, Liverpool Hospital, Locked Bag 7103, Liverpool BC, NSW 1871, Australia. melissa@unsw.edu.au.
authors.forename: Melissa
authors.initials: M
authors.lastname: Leung
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Wong
authors.forename: Stephane
authors.initials: S
authors.lastname: Heritier
authors.forename: Anastasia S
authors.initials: AS
authors.lastname: Mihailidou
authors.forename: Dominic Y
authors.initials: DY
authors.lastname: Leung
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002985:Clinical Protocols; D003094:Collagen / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D058065:Diabetic Cardiomyopathies / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D003971:Diastole; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D000077545:Eplerenone; D005355:Fibrosis; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009517:New South Wales; D011446:Prospective Studies; D020127:Recovery of Function; D012107:Research Design; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013599:Systole; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D003094:Collagen